In response to the program announcement for Phase IIb proposals for complex, in-vitro brain and behavior tools (PA-11-135), this proposed study automates all aspects of in-vitro Microelectrode Array (MEA) technology to deliver the first ever high throughput MEA-based screening system. This development will not only enable rapid advancements in the study of basic network-level electrophysiology, but it will also create new opportunities for CNS disease modeling and phenotypic screening. This Phase IIb proposal involves two significant developments for neurological research, both building on the commercialized 768-channel multiwell MEA system developed in Phase II. Specifically, Aim 1 automates compound administration and experiment management to produce a turnkey platform for dosing neural culture as well as capturing, com- pressing, and storing network electrophysiological datasets. Among its many advantages, this platform will recover signals traditionally obscured by stimulation artifacts. This capability, combined with the ability to simultaneously manage 768 microelectrodes and automate experimental protocols, will capture single-cell and network-level neural activity at unparalleled rates. In addition, Aim 2 will automate the analysis of the immense volumes of continuous, data traces generated by the Aim 1 developments, translating massive raw datasets into meaningful metrics that accurately reflect the interactions between networks of cells. Ultimately, the final MEA screening platform will provide automated liquid handling, user-friendly experiment tools, and sophisticated neural analysis software. For scientists, this integration will significantly improve their ability to extact functional information from neural cultures; paving the way for new progress in drug discovery, safety assessment, and basic science.